Submissions for variant NM_003060.4(SLC22A5):c.59T>A (p.Leu20His)

gnomAD frequency: 0.00362  dbSNP: rs144020613

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000022299	SCV000632558	benign	Renal carnitine transport defect	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000838010	SCV000979874	benign	not provided	2019-01-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194405	SCV001363924	benign	not specified	2019-03-11	criteria provided, single submitter	clinical testing	Variant summary: SLC22A5 c.59T>A (p.Leu20His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 275576 control chromosomes, predominantly at a frequency of 0.012 within the African subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 3-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in SLC22A5 causing Systemic Primary Carnitine Deficiency phenotype (0.0046), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. c.59T>A has been reported in the literature in a cohort of subjects with a possible carnitine deficiency (Frigeni_2017). A functional study, Frigeni_2017, cites the variant with a transport activity of 46.77%, which the authors classify the variant as benign. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV000022299	SCV002055865	benign	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing
Giacomini Lab, University of California, San Francisco	RCV000022299	SCV002576681	uncertain significance	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
CeGaT Center for Human Genetics Tuebingen	RCV000838010	SCV004161363	benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	SLC22A5: BS1, BS2